Comparison of various treatments for experimentally induced equine infectious arthritis

Abstract

SUMMARY To evaluate the effects of 5 treatments on clinical responses, synovial fluid analysis, radiographic changes, bacteriologic culture results of the synovial fluid and synovial membrane, microscopic characteristics of the synovial membrane, and articular cartilage histochemistry, Staphylococcus aureus organisms (1.6 × 10 6 colony-forming units) were inoculated into the tarsocrural joints of 12 horses (n = 24 joints; 2 joints/horse). Each horse was given phenylbutazone (2 g) orally, every 24 hours, beginning 24 hours after inoculation. Two horses (ie, 4 joints) were not given other treatment (controls; group 1). All other horses (ie, 20 joints) were given a trimethoprim-sulfadiazine combination orally, once daily (30 mg/kg; 8 joints) or twice daily (30 mg/kg q 12 hr; 12 joints). Each of these 20 joints were assigned to 1 of 5 treatment groups (4 joints/group) in a balanced incomplete block design. Group 2 (4 joints) was given only the antibiotics once daily. Twelve joints were treated by through-and-through joint lavage on day 1 (group 3), days 1 and 3 (group 4), or days 1, 3, and 6 (group 5). Joints in group 6 had an arthrotomy performed on day 1, with subsequent lavage via an indwelling drain every 12 hours for 4 days. In groups 3 through 6, 1 joint in each group was treated with antibiotics once daily, and 3 joints were treated with antibiotics twice daily. All horses were clinically assessed each day. Complete blood count was performed on days 3, 6,10, and 21. Before inoculation and on days 0, 1, 3, 6, 10, and 21, synovial fluid specimens were collected and analyzed for color, clarity, total protein concentration, wbc count, differential count, and mucin clot-forming ability. Synovial fluid specimens were cultured bacteriologically before inoculation and on days 0 and 21. Horses in group 1 (controls) were euthanatized before day 6. All other horses were euthanatized on day 21. Tarsocrural joints were opened and examined. Synovial membrane specimens were bacteriologically cultured. Synovial membrane specimens were examined histologically (hemotoxylin and eosin stain) and articular cartilage specimens were (safranin O fast green stain) evaluated histochemicallv. Synovial membrane specimens were histologically graded into 5 categories. Intensity of articular cartilage intercellular staining with safranin 0 was graded for superficial, outer intermediate, inner intermediate, and deep zones. Two-way analysis of variance was performed to evaluate differences among groups and across time for the determinants evaluated. A 1-way analysis of variance was performed to evaluate differences in the peripheral clinicopathologic determinants across time and to evaluate histologic and histochemic differences among groups. To determine significance, the probability of a type-I error was < 0.05. Horses with joints assigned to group 2 (administered antibiotics once daily) had intermittent pyrexia. Differences in other clinical determinants were not detected among treatment groups. All horses had a low pcv , high plasma fibrinogen concentrations, and high peripheral wbc counts between days 3 and 10. The tarsocrural joints did not have radiographic evidence of bone erosion or new bone formation. In joints in which an arthrotomy was performed, less soft tissue swelling was apparent on day 10, compared with other treatment groups ( P = 0.1). Synovial fluid was flocculent after day 3 in all groups, except group 6 (arthrotomy). On day 21, joints in group 6 had a higher ( P = 0.01) synovial fluid protein concentration than did joints in groups 2 or 3. Differences in synovial fluid, wbc count, differential count, or mucin clot-forming ability were not detected among the groups. At the termination of the study, Staphylococcus aureus was isolated from the synovial fluid and from the synovial membrane specimens of 87% of the joints treated with once-daily administration of antibiotics and of 42% of the joints treated with twice-daily administration of antibiotics ( P < 0.05). Joint drainage (groups 3 through 6) did not affect bacteriologic isolation rates. Synovial membrane specimens from joints in which an arthrotomy was performed had significantly less histologic evidence of inflammation ( P < 0.05), compared with other treatment groups. Articular cartilage specimens from joints treated with antibiotics once daily and for which joint drainage was not performed (group 2) had less intense intercellular staining with safranin O (ie, greater loss of glycosaminoglycans) than did other treatment groups. Systemic administration of antibiotics (even in low doses, ie, administered once daily) resulted in clinical improvement in appetite, comfort, and other clinical determinants measured, compared with control horses. Treatment with higher doses of antibiotics (ie, administered twice daily) decreased the rate of bactériologie isolation, and, with joint drainage, resulted in less loss of articular cartilage glycosaminoglycans (ie, significantly greater staining intensity with safranin O) than joints treated with antibiotics once daily. Arthrotomy with lavage resulted in less synovitis and less fibrin formation than treatment by through-and-through lavage performed 1 to 3 times. Delayed healing, fibrosis, and excessive granulation tissue complicated healing of all arthrotomy incisions. Rates of bacterial isolation were identical from synovial fluid specimens and from synovial membrane specimens.